PerkinElmer's Contract Research Services has assay development programs directed toward serving the science needs of our clients using the most appropriate detection methods for a given molecular target and screening objective. PerkinElmer's Contract Research Services develops on average more than 100 new assays per year for its clients and its screening service business. Our broad instrumentation platforms also allow more flexibility to perform your assays here at PerkinElmer's Contract Research Services on an exclusive, outsourced basis. Our core capabilities including experience in compound profiling and high throughput screening provide an expansive range of assay technologies to serve your assay development efforts. These programs focus on several major areas of interest.
General Assay Development
Common targets for these types of assays include both GPCRs and other membrane bound receptors, nuclear receptors, DNA-transcription factors and siRNA. Standard platforms include Radioligand Binding, Time Resolved Fluorescence (TRF), Fluorescence Polarization (FP), Fluorescence Resonance Energy Transfer (FRET), Alpha Screen, Luminescence/Absorbance, Scintillation Proximity Assays (SPA)* and Scintillating Microplates
A wide range of enzyme assays can be developed using either endogenous cellular enzymes or recombinant ones. The assays can be developed to simply measure compound inhibition or changes in kinetics or expression levels. Technologies employed for these types of assays include PerkinElmer's Microfluidic Platform, Radioactive and Fluorescent Label Substrate Microplate Conversion Measurements, HPLC and LC-MS.
Both channel binding sites and ion fluxes can be tracked in custom in vitro systems to measure compound interactions with ion channels. Approaches range from an assessment of ligand interacts with these sites to actual ion flows using fluorescent dyes, radioactive ions, flame photometry and automated whole cell patch clamping.
Functional readouts from cellular responsive elements can be measured in a variety of formats including signal transduction through customized transfected reporter genes in a cell. These assays can be developed to provide High Content information using multiple readouts from a single screening. Cell readouts can typically determined with second messenger reporter systems, transport across membranes, ELISAs, RT PCR, Protein Arrays, and whole cell responses such as migration and proliferation.
Functional cellular response is a complex multi-step biological process that can be measured utilizing several techniques. Here at PerkinElmer's Contract Research Services we are utilizing the latest, state of the art assay platforms such as Luminex, flowcytometry, planar protein and gene expression arrays, high throughput Western blotting, multiplex qRT-PCR and many others. Through successful implementation of these methods we are offering complete custom build solutions to measure cellular responses at each step of the cell activation cascade, such as:
- Intracellular protein phosphorylation
- Transcription factor activation (DNA binding activity and reporter assays)
- Gene expression, (qRT-PCR and gene expression arrays)
- Protein expression (including cytokines, chemokines and growth factors)
- Each of these readouts can be evaluated individually or can be
- incorporated into multi parameter assay system thus increasing throughput and informational content of each assay run.
Compound effects on the function and viability of a wide array of tumor and primary human and rodent cell lines can be measured with a series of custom assays to measure the integrity of cells. These can range from multiple endpoints for cell viability to functional readouts from any set of chosen biomarkers.
Kinase Assay Development
Kinases are one of the most important classes of enyzmes and are involved in signal transduction and signaling networks within cells. These kinase signaling pathways play a fundamental role in regulating cell proliferation, cell metabolism and cell death. Research shows that changes in protein kinase activity within a cell can lead to several disease states, most notably cancer. With this knowledge base, scientists have been investigating the ability of drugs to block various protein kinases as a cancer therapy. This approach has proved successful with the discovery of several kinase inhibitor drugs for the treatment of various cancers such as Gleevec®, Iressa® and Tarceva®. In addition to their involvement in cancer, protein kinases are implicated in diabetes, inflammation and neurological development and degeneration.
Because protein kinases are involved in a wide variety of disease states, over 30% of all spending for drug development focuses on this area of research. Through the use of the PerkinElmer's LabChip® microfluidic platform, we can develop specialized kinase assays to assist you in accelerating and optimizing your lead identification efforts in this area.
Advantages of Kinase Assay Development using microfluidics:
- Enzymology studies available with real time kinetics
- Direct measurement of both phosphorylated & unphosphorylated peptide
- Improved data quality and precision when compared to traditional methods
- High signal-to-noise ratio
- Identification of weak enzyme inhibitors
- Increased Z' values (range of 0.8 - 0.9)
- Non-radioactive, antibody free format
- High throughput screening format
High Throughput & Library Screening
PerkinElmer's Contract Research Services provides high throughput screening (HTS) services for primary discovery of compound libraries at relevant therapeutic targets on a customized basis.
High Throughput Screening
We can provide an HTS assay based on most of the molecular targets included in PerkinElmer's Contract Research Services's portfolio of developed and validated assays, transfer of a proprietary assay from the client to PerkinElmer's Contract Research Services, or through development of an HTS assay de novo based on a novel target.
PerkinElmer's Contract Research Services understands the need to ensure that the development of lead compounds has the greatest success in vivo. We have recently expanded our services to include synthetic medicinal chemistry for lead optimization solutions to support your drug discovery programs. Our chemistry services include:
- design of virtual chemical libraries according to feasible synthetic routes and schemes
- in silico selection of focused chemical libraries optimized for pharmacological properties
- actual library preparations using parallel synthesis
All synthetic chemicals are purified (95%) and characterized before committed to in vitro screening
Our data management and tracking systems, based on ActivityBase (IDBS), provide PerkinElmer's Contract Research Services the tools for industry standard reporting formats and electronic data transfer.
Primary screening programs can smoothly progress to a full hit-to-optimized-lead solution through the integration of PerkinElmer's Contract Research Services's secondary screening services.
PerkinElmer's Contract Research Services offers rapid data turnaround, flexible assay formats, and high quality data that the industry demands, all at a price that is competitive with in-house costs. Outsourcing projects to PerkinElmer's Contract Research Services can eliminate the need for costly infrastructure investments for our client's HTS needs. For more information on our high throughput screening and chemistry services, contact your PerkinElmer's Contract Research Services representative.